The oral ingestion of solid medicament forms (especially of tablets and capsules) is accompanied by numerous problems for children and older people. Children must be 6 to 8 years old before they can reliably swallow solid medicament forms, there being major restrictions concerning the size of the medicament forms. Older people often suffer from swallowing disorders, too, which are caused by a decrease in saliva formation in old age so that the solid medicament forms may be swallowed only with difficulty. They react with reluctance to the regular ingestion often necessary over many years which frequently leads to irregular compliance.
In an attempt to solve these problems, numerous alternatives have been offered in the market place. However, tablets for chewing or sucking and orodispersible tablets are not a genuine alternative either, especially for young children. Due to dental problems, older people often have an aversion against chewable tablets, too, and sucking tablets or orodispersible tablets are not convincing either due to reduced salivation. In addition, an expensive and complicated step is necessary to first convert the active ingredients which often have a bitter taste into small saliva-resistant particles before they are processed into chewable tablets, sucking tablets or orodispersible tablets, the masking of the taste often being more or less destroyed by the subsequent necessary compression to tablets with the result that the bitter taste often leads to an aversion against this medicament form. The processing of release-controlled enteric-coated or retarded particles into the above medicament forms is even more problematic. Again, the subsequent compaction causes at least partial destruction of the coating layer. As a result, formulators attempt to protect the saliva-resistant particles by a large amount of adjuvants which are easily compressed. This, in turn, raises the cost of preparing these tablets and increases the tablet size unnecessarily.
Therefore, there are granules and powders on the market which usually must be converted into a suspension with a certain amount of water before ingestion. In most cases, such suspensions require preservation, must be kept in the refrigerator and generally entail high production costs. Often mistakes are made when the suspension is prepared. By foaming or insufficient agitation before application, problematic dosing errors may occur, and especially older people have problems with this dosage form.
With young children or adults with swallowing disorders, a syrup is often chosen as an alternative. In many cases, however, problems occur because the active ingredient is very bitter. Syrups must always be protected by preservatives which have an inherent allergy risk. In many active ingredients, stability problems occur when they are processed into an aqueous syrup.
U.S. Pat. No. 4,882,169 proposes coated pellets having a diameter of 0.2 to 3 mm which allegedly form a homogeneous dispersion in water. The particles contain at least one pharmaceutically active substance, optionally one or more release-controlling or taste-masking coatings and one swellable outer layer. The latter contains a swellable polymer, preferably guar, and a binder. Together with guar granules and flavouring agents, the coated pellets are bagged into sachets from which they are taken and dispersed in water.
U.S. Pat. No. 5,288,500 proposes to combine a plurality of particles containing the active ingredient having a diameter of 0.05 to 7 mm with a gelling or swelling agent. The latter may be present in admixture with the particles containing the active ingredient, be contained on a coating, be added to the particles containing the active ingredient before admixing with an aqueous carrier or be dispersed in an aqueous carrier to which the particles containing the active ingredient are admixed. The proposed formulation is dispersed in an aqueous carrier. In particular, hydrophilic polymers forming colloidal dispersions, sols or suspensions in an aqueous environment are indicated as gelling or swelling agents for the formulations proposed in U.S. Pat. No. 5,288,500. The polymers are used in an amount sufficient to ensure that dispersal in an aqueous carrier is not impaired. If desired, the viscosity in the immediate vicinity of the dispersed particles may be influenced by the formation of salt, chelation, changes of polarity and such like. The components of the formulation may be kept separate until they are processed or bagged into sachets or processed to tablets or capsules.
The formulations described in U.S. Pat. No. 4,882,169 and U.S. Pat. No. 5,228,500 are ingested together with an aqueous carrier wherein they must be dispersed before administration. In this process, the formulations disintegrate into individual particles so that quantitative ingestion is not guaranteed as a rule. This is because, in general, drinking a particle suspension or dispersion is a real problem, for after the solution has been drunk a residue of the particles is usually left on the bottom of the vessel and can be brought into the mouth with difficulty only. It is not at all sure either whether the patient will even try to do this. Sedimentation of the particles may be prevented partially only by drinking the particle suspension very quickly after stirring. Such a medicament form which requires fast drinking is particularly unsuitable for young children and older patients.
Formulations according to the two cited patents have the disadvantage that quantitative ingestion in the prescribed dose is generally not guaranteed and that they must be predispersed in an aqueous carrier first, i.e. clean drinking water and a suitable vessel must be available which renders ingestion difficult, especially when travelling.
An improved agent is disclosed in WO 98/06385. The printed publication describes a pharmaceutical composition in the form of particles which may be ingested directly even without liquid. The pharmaceutical composition is for oral administration and contains one or more coated active ingredient particles having a coating consisting of one or more layers, the composition of the coating being characterised in that    a) the coating layer or coating layers contain at least one hydratable polymer which, upon contact with saliva or water, forms a continuous, mouldable, viscous sticky particle mass which prevents particles containing the active ingredient from escaping from this mass and the release of the active ingredient in the oral cavity, and    b) the outer coating layer contains an effective amount of at least one agent which promotes salivation.
It is the disadvantage of that invention that it is difficult for young children and older people to keep the particles poured onto the tongue together until saliva combines the individual particles into a particle mass. Especially children will distribute the polymer-coated particles in the mouth and the saliva formed is insufficient for the particles sticking to the surface to be swallowed without the aid of water. Since the particles poured into the mouth often do not or not sufficiently stick together in a particle mass, the release of the active ingredient from the particles is increased so that there is only insufficient protection against the unpleasant bitter taste of the active ingredient. This active ingredient may diffuse much more easily from individual particles than from a sticky lump of particles with a much reduced surface releasing the active ingredient. It is the objective of this development of the prior art to generate only that amount of saliva sufficient to make the polymers sticky on the surface so that they form a lump. It is not an objective of the development to cause major spontaneous salivation immediately after ingestion which would facilitate swallowing tasteprotected particles. Only if the particles poured onto the middle of the tongue are skilfully pressed against the palate for approx. 30 to 60 seconds will they agglutinate, forming a continuous, mouldable, viscous particle paste which may be swallowed with comparative ease. Also, it has been shown that a practically quantitative agglutination of the individual particles is never achieved and individual particles diffuse into the oral cavity, for instance between the teeth, which is a disadvantage.
Especially with children, it is of particular importance that a mechanically stable, soft particle surface is quickly formed upon contact with saliva which cannot be removed by tongue movement and gives the particles a pleasant feel in the mouth. In general, hard granules, coarser crystals, but also pellets are perceived as unpleasant foreign bodies in the mouth because of their rough surface. Especially with young children, this will lead to a refusal to ingest or swallow these particles, or the children will try to spit them out. Therefore, it is important that a soft, but mechanically stable surface is formed on these particles within seconds after ingestion. Especially for children, it is difficult to swallow the particles containing the active ingredient quickly and in the right quantity. Rather, they will tend to distribute the particles through the entire oral cavity. In addition, uncontrolled tongue movements will exert a strong mechanical stress on the particle surface so that a swollen, unfixed polymer present on the surface is easily rubbed off and the rough particle surface which is perceived as unpleasant re-emerges.
To ensure that especially young children will swallow a pharmaceutical composition in particulate form without undue persuasion, it is important that these particles do not cause a sandy, hard, grainy, unpleasant feeling in the mouth, but have a mechanically stable, soft, non-sticky surface which forms very quickly.